POS0973 EFFECT OF RENAL AND EXTRARENAL FLARES ON DEVELOPMENT OF CKD AND EXTRARENAL ORGAN DAMAGE IN PATIENT WITH LUPUS NEPHRITIS
Authors: C. Cruciani, M. Gatto, G. Frontini, M. Calatroni, F. Reggiani, B. Trezzi, L. Iaccarino, R. A. Sinico, A. Doria, G. Moroni
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with a plethora of manifestations potentially affecting every organ system. Lupus nephritis (LN) is recognized as one of the most common and fearsome manifestations presenting in up to 35-60% of SLE patients, usually during the first 5 years from disease onset<sup>[1]</sup>. LN and LN flares are associated with nephron loss and chronic kidney disease (CKD)<sup>[1,2,3]</sup>, which on its own is a major risk factor for overall morbidity and mortality<sup>[1,4]</sup>. However, the association between extrarenal disease flares and CKD and the contribution of LN and extrarenal flares to overall damage accrual are less investigated. <h3>Objectives</h3> To assess the impact of disease flares on development of CKD and extrarenal organ damage in lupus nephritis. <h3>Methods</h3> We performed a multicentric retrospective cohort study on biopsy-proven LN patients in whom we evaluated the impact of disease flares on CKD development and damage accrual. Disease flares were divided into renal (doubling of serum creatinine or persistent increase in proteinuria with normal GFR) and extra-renal (cSLEDAI&gt;0 across extrarenal domains). Renal-extrarenal clinical remission was defined as serum creatinine &lt;1mg/dl, eGFR&gt;60ml/min/1.73m2, proteinuria &lt;0.5g/24h and cSLEDAI=0 lasting for at least one year. CKD as serum creatinine &gt;1.0mg/dl with eGFR &lt;60ml/min/1.73 m2 and inactive urinary sediment, confirmed by at least three determinations for at least 3 months, and damage was measured by the SLICC damage index (SDI). Non-parametric tests were used for comparisons. <h3>Results</h3> 303 LN patients were included (females 86.5%, mean follow-up 14.8 (9.8-22.0) years). 257 patients (84.8%) achieved remission after a median of 1.44 (0.69-3.58) years from initial treatment, which persisted throughout follow-up in 115 patients. Among 142 patients who had their remission interrupted, 39 (27.5%) did so due to extrarenal flares, while 103 (72.5%) experienced renal flares (creatinine or proteinuria). Loss of remission due to extrarenal flares was less frequently associated with CKD development than remission lost to renal flares (5.1% vs. 28.2%, respectively; OR95%CI 0.14 (0.031-0.61), p=0.003), while the ultimate median annual SDI increase was comparable between patients experiencing either renal or non–renal flares (renal vs. extrarenal flares: +0.05 (0-0.1) vs. +0.06 (0-0.14), p=0.8). <h3>Conclusion</h3> Patients experiencing renal flares are at greater risk of CKD, yet more than 5% of patients undergoing extrarenal flares develop CKD. Renal and extrarenal flares both contribute comparably to damage accrual across other organ domains. Extra-renal flares deserve attention and should not be regarded as mild by definition. <h3>References</h3> [1]Anders, H.-J. <i>et al.</i> Lupus nephritis. <i>Nat Rev Dis Primers</i><b>6</b>, 7 (2020). [2]Moroni, G., Quaglini, S., Maccario, M., Banfi, G. &amp; Ponticelli, C. "Nephritic flares" are predictors of bad long-term renal outcome in lupus nephritis. <i>Kidney Int</i><b>50</b>, 2047–2053 (1996). [3]Mejía-Vilet, J. M. <i>et al.</i> Renal flare prediction and prognosis in lupus nephritis Hispanic patients. <i>Lupus</i><b>25</b>, 315–324 (2016). [4]Mageau, A. <i>et al.</i> The burden of chronic kidney disease in systemic lupus erythematosus: A nationwide epidemiologic study. <i>Autoimmun Rev</i><b>18</b>, 733–737 (2019). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.